Induced Chirality in Sulfasalazine by Complexation With Albumins: Theoretical and Experimental Study

Area of Science:

• Biochemistry and Molecular Biology
• Pharmacology and Drug Discovery
• Computational Chemistry

Background:

• Drugs interact with circulating macromolecules like serum albumin, a key transport protein.
• Sulfasalazine (SSZ) is known to bind to drug site 1 (DS1) on human serum albumin (HSA) and bovine serum albumin (BSA).
• Understanding these interactions is crucial for drug efficacy and safety.

Purpose of the Study:

• To investigate the differences in sulfasalazine complexation with human serum albumin (HSA) and bovine serum albumin (BSA) at drug site 1 (DS1).
• To elucidate the conformational behavior of SSZ when bound to HSA versus BSA.
• To correlate spectroscopic and computational findings with protein-environment interactions.

Main Methods:

• Spectroscopic techniques: Ultraviolet-visible absorption (UV-Vis) and Electronic Circular Dichroism (ECD).
• Theoretical methodologies: Time-Dependent Density Functional Theory (TD-DFT) and molecular docking simulations.
• Comparative analysis of SSZ interaction sites and conformational states within HSA and BSA.

Main Results:

• Significant differences were observed in UV-Vis and ECD spectra for SSZ complexation with HSA and BSA.
• Molecular docking and TD-DFT suggest distinct SSZ conformations within the DS1 of HSA and BSA.
• These conformational differences lead to varied exposure of SSZ to different amino acid residues and hydrophobic environments.

Conclusions:

• The conformation of SSZ within the DS1 site of HSA and BSA differs, impacting its interaction profile.
• Variations in SSZ conformation may be influenced by the specific binding site characteristics or protein dynamics.
• SSZ exhibits less conformational freedom in HSA compared to BSA, potentially due to size constraints within the binding pocket.